EP2786985A3 - Antagonists of the glucagon receptor - Google Patents

Antagonists of the glucagon receptor Download PDF

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Publication number
EP2786985A3
EP2786985A3 EP14162609.3A EP14162609A EP2786985A3 EP 2786985 A3 EP2786985 A3 EP 2786985A3 EP 14162609 A EP14162609 A EP 14162609A EP 2786985 A3 EP2786985 A3 EP 2786985A3
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EP
European Patent Office
Prior art keywords
glucagon receptor
receptor antagonist
antagonists
present
provides
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP14162609.3A
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German (de)
French (fr)
Other versions
EP2786985A2 (en
EP2786985B1 (en
Inventor
Jorge E. Gomez-Galeno
Raja K. Reddy
Paul D. Van Poelje
Robert Huerta Lemus
Thanh Huu Nguyen
Matthew P. Grote
Qun Dang
Scott J. Hecker
Venkat Reddy Mali
Mingwei Chen
Zhili Sun
Serge Henri Boyer
Haiqing Li
William Craigo
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Metabasis Therapeutics Inc
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Metabasis Therapeutics Inc
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Publication of EP2786985A2 publication Critical patent/EP2786985A2/en
Publication of EP2786985A3 publication Critical patent/EP2786985A3/en
Application granted granted Critical
Publication of EP2786985B1 publication Critical patent/EP2786985B1/en
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    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
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    • C07C2601/00—Systems containing only non-condensed rings
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    • C07C2601/14—The ring being saturated
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    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present invention provides for novel compounds of Formula I and pharmaceutically acceptable salts and co-crystals thereof which have glucagon receptor antagonist or inverse agonist activity. The present invention further provides for pharmaceutical compositions comprising the same as well as their use in methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucagon receptor antagonist is indicated, including Type I and II diabetes, insulin resistence and hyperglycemia.
EP14162609.3A 2007-02-09 2008-02-11 Antagonists of the glucagon receptor Not-in-force EP2786985B1 (en)

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Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5322951B2 (en) 2007-02-09 2013-10-23 リガンド・ファーマシューティカルズ・インコーポレイテッド Novel antagonist of glucagon receptor
KR101599089B1 (en) 2008-08-13 2016-03-02 메타베이시스 테라퓨틱스, 인크. Glucagon antagonists
WO2010019828A1 (en) * 2008-08-13 2010-02-18 Metabasis Therapeutics, Inc. Glucagon receptor antagonists
US20110281795A1 (en) 2009-01-28 2011-11-17 Songnian Lin Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
EP2330137B1 (en) * 2009-12-04 2013-06-26 LANXESS Deutschland GmbH Methylenaminoethylsulfonic acids-chelate resins
WO2011107494A1 (en) 2010-03-03 2011-09-09 Sanofi Novel aromatic glycoside derivatives, medicaments containing said compounds, and the use thereof
JP5603487B2 (en) 2010-06-10 2014-10-08 テクニオン リサーチ アンド ディベラップメント ファウンデイション リミテッド Process for the preparation of iodide
EP2582709B1 (en) 2010-06-18 2018-01-24 Sanofi Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases
US8530413B2 (en) 2010-06-21 2013-09-10 Sanofi Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments
TW201215387A (en) 2010-07-05 2012-04-16 Sanofi Aventis Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament
TW201221505A (en) 2010-07-05 2012-06-01 Sanofi Sa Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament
TW201215388A (en) 2010-07-05 2012-04-16 Sanofi Sa (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments
AU2011346670B2 (en) 2010-12-23 2015-05-07 Pfizer Inc. Glucagon receptor modulators
WO2012107850A1 (en) 2011-02-08 2012-08-16 Pfizer Inc. Glucagon receptor modulator
US8927577B2 (en) 2011-07-22 2015-01-06 Pfizer Inc. Quinolinyl glucagon receptor modulators
WO2013037390A1 (en) 2011-09-12 2013-03-21 Sanofi 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
WO2013045413A1 (en) 2011-09-27 2013-04-04 Sanofi 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
US8859098B2 (en) * 2012-05-18 2014-10-14 Lord Corporation Acrylic adhesion promoters
TW201427658A (en) 2012-12-10 2014-07-16 Merck Sharp & Dohme Methods of treating diabetes by administering a glucagon receptor antagonist in combination with a cholesterol absorption inhibitor
JP2017519000A (en) 2014-06-12 2017-07-13 リガンド・ファーマシューティカルズ・インコーポレイテッド Glucagon antagonist
WO2017004383A1 (en) * 2015-06-30 2017-01-05 Dana-Farber Cancer Institute, Inc. Inhibitors of egfr and methods of use thereof
CN106336387A (en) * 2015-07-10 2017-01-18 浙江海正药业股份有限公司 Amides derivative, preparation method thereof and purpose of amides derivative on medicine
CN105001174A (en) * 2015-07-14 2015-10-28 佛山市赛维斯医药科技有限公司 Compound containing benzisoxazole and tail end cyano benzyl group structure as well as application of compound
CN104987314A (en) * 2015-07-14 2015-10-21 佛山市赛维斯医药科技有限公司 Compound containing benzisoxazole and structure with nitryl and benzyl groups at the tail end and application thereof
CN105384703A (en) * 2015-10-29 2016-03-09 河南大学 Thiazolidinedione chemical compound preparation method
CN109071420B (en) * 2016-06-14 2021-06-18 上海昂睿医药技术有限公司 Amide derivatives, preparation method and medical application thereof
US20190194143A1 (en) * 2016-08-17 2019-06-27 Ligand Pharmaceuticals, Inc. Glucagon receptor antagonists
SG10201913074WA (en) 2016-08-30 2020-03-30 Regeneron Pharma Methods of treating severe insulin resistance by interfering with glucagon receptor signaling
EP3529278A1 (en) 2016-10-20 2019-08-28 Regeneron Pharmaceuticals, Inc. Methods of lowering blood glucose levels
PT3573611T (en) * 2017-01-24 2022-03-15 Alphala Co Ltd Amide compounds and use thereof
CA3071387A1 (en) 2017-08-22 2019-02-28 Regeneron Pharmaceuticals, Inc. Methods of treating urea cycle disorders by interfering with glucagon receptor signaling
TW202003453A (en) 2018-02-13 2020-01-16 美商利根德製藥公司 Glucagon receptor antagonists

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003048109A1 (en) * 2001-12-03 2003-06-12 Novo Nordisk A/S Novel glucagon antagonists
WO2004002480A1 (en) * 2002-06-27 2004-01-08 Novo Nordisk A/S Novel glucagon antagonists/inverse agonists

Family Cites Families (86)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3524846A (en) 1967-06-02 1970-08-18 Syntex Corp Process for the didealkylation of phosphonate esters
US3536809A (en) 1969-02-17 1970-10-27 Alza Corp Medication method
US3598123A (en) 1969-04-01 1971-08-10 Alza Corp Bandage for administering drugs
US3845770A (en) 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US3916899A (en) 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
JPS5322951B2 (en) 1974-06-05 1978-07-12
US4008719A (en) 1976-02-02 1977-02-22 Alza Corporation Osmotic system having laminar arrangement for programming delivery of active agent
JPS55100859A (en) 1979-01-16 1980-08-01 Kikai Syst Shinko Kyokai Dummy bar containing device
IE58110B1 (en) 1984-10-30 1993-07-14 Elan Corp Plc Controlled release powder and process for its preparation
US4968788A (en) 1986-04-04 1990-11-06 Board Of Regents, The University Of Texas System Biologically reversible phosphate and phosphonate protective gruops
US5091552A (en) 1986-06-30 1992-02-25 Board Of Regents, The University Of Texas System Novel antitumor aldophosphamide analogs
JPH0738070B2 (en) * 1986-07-25 1995-04-26 富士写真フイルム株式会社 Silver halide photographic light-sensitive material
DE3860351D1 (en) * 1987-03-09 1990-08-30 Eastman Kodak Co PHOTOGRAPHIC SILVER HALOGENIDE MATERIALS AND METHOD THAT CONTAINS A PYRAZOLOAZOLE COUPLER.
JPH081079B2 (en) 1987-10-12 1996-01-10 大和ハウス工業株式会社 Multi-story structure
JPH01197740A (en) * 1988-02-01 1989-08-09 Konica Corp Silver halide photographic sensitive material
US5073543A (en) 1988-07-21 1991-12-17 G. D. Searle & Co. Controlled release formulations of trophic factors in ganglioside-lipsome vehicle
IT1229203B (en) 1989-03-22 1991-07-25 Bioresearch Spa USE OF 5 METHYLTHETRAHYDROPHOLIC ACID, 5 FORMYLTHETRAHYDROPHOLIC ACID AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS IN THE FORM OF CONTROLLED RELEASE ACTIVE IN THE THERAPY OF MENTAL AND ORGANIC DISORDERS.
US5120548A (en) 1989-11-07 1992-06-09 Merck & Co., Inc. Swelling modulated polymeric drug delivery device
US5733566A (en) 1990-05-15 1998-03-31 Alkermes Controlled Therapeutics Inc. Ii Controlled release of antiparasitic agents in animals
CA2083386C (en) 1990-06-13 1999-02-16 Arnold Glazier Phosphorous prodrugs
US5157027A (en) 1991-05-13 1992-10-20 E. R. Squibb & Sons, Inc. Bisphosphonate squalene synthetase inhibitors and method
US5580578A (en) 1992-01-27 1996-12-03 Euro-Celtique, S.A. Controlled release formulations coated with aqueous dispersions of acrylic polymers
US5591767A (en) 1993-01-25 1997-01-07 Pharmetrix Corporation Liquid reservoir transdermal patch for the administration of ketorolac
ATE199906T1 (en) 1993-06-29 2001-04-15 Mitsubishi Chem Corp PHOSPHONATE NUCLEOTIDE ESTER DERIVATIVES
IT1270594B (en) 1994-07-07 1997-05-07 Recordati Chem Pharm CONTROLLED RELEASE PHARMACEUTICAL COMPOSITION OF LIQUID SUSPENSION MOGUISTEIN
US5780058A (en) 1995-07-21 1998-07-14 Alza Corporation Oral delivery of discrete units
US6132420A (en) 1996-02-02 2000-10-17 Alza Corporation Osmotic delivery system and method for enhancing start-up and performance of osmotic delivery systems
JPH09241284A (en) 1996-03-08 1997-09-16 Koji Yamashita New oxyazaphosphorine derivative
MY125849A (en) 1997-07-25 2006-08-30 Alza Corp Osmotic delivery system, osmotic delivery system semipermeable body assembly, and method for controlling delivery rate of beneficial agents from osmotic delivery systems
JPH1197740A (en) 1997-09-19 1999-04-09 Showa Denko Kk Epitaxial wafer for gap light emitting diode and gap light emitting diode
EP1041975B1 (en) 1997-12-22 2002-09-04 Alza Corporation Rate controlling membranes for controlled drug delivery devices
AU1828599A (en) 1997-12-29 1999-07-19 Alza Corporation Osmotic delivery system with membrane plug retention mechanism
ATE248002T1 (en) 1997-12-31 2003-09-15 Alza Corp SYSTEM FOR MONITORING AN OSMOTIC DRUG DELIVERY DEVICE
US6245357B1 (en) 1998-03-06 2001-06-12 Alza Corporation Extended release dosage form
US6365185B1 (en) 1998-03-26 2002-04-02 University Of Cincinnati Self-destructing, controlled release peroral drug delivery system
RU2246295C2 (en) 1998-11-02 2005-02-20 Элзэ Копэрейшн Medicinal formulation with constant rate for releasing medicinal substance, core of medicinal formulation and method for providing relieved release of medicinal substance from medicinal formulation
US6375975B1 (en) 1998-12-21 2002-04-23 Generex Pharmaceuticals Incorporated Pharmaceutical compositions for buccal and pulmonary application
US6342249B1 (en) 1998-12-23 2002-01-29 Alza Corporation Controlled release liquid active agent formulation dosage forms
US6503949B1 (en) 1999-05-17 2003-01-07 Noro Nordisk A/S Glucagon antagonists/inverse agonists
JP2002544254A (en) 1999-05-17 2002-12-24 ノボ ノルディスク アクティーゼルスカブ Glucagon antagonist / inverse agonist
AU5723500A (en) * 1999-05-24 2000-12-12 Cor Therapeutics, Inc. Inhibitors of factor xa
WO2001019830A1 (en) 1999-09-10 2001-03-22 Novo Nordisk A/S MODULATORS OF PROTEIN TYROSINE PHOSPHATASES (PTPases)
DE10008329A1 (en) 2000-02-23 2001-08-30 Merck Patent Gmbh New aminosulfonyl-biphenyl derivatives are Factor Xa and Factor VIIa inhibitors useful e.g. for treating thrombosis, myocardial infarction, arteriosclerosis, inflammation or angina pectoris
HUP0301501A2 (en) * 2000-06-23 2003-08-28 Novo Nordisk A/S Glucagon antagonists/inverse agonists, pharmaceutical compositions containing them and their use for preparation of pharmaceutical compositions
AU2002223501A1 (en) 2000-11-17 2002-05-27 Agouron Pharmaceuticals, Inc. Glucagon antagonists/inverse agonists
US6881746B2 (en) 2001-12-03 2005-04-19 Novo Nordick A/S Glucagon antagonists/inverse agonists
US6762318B2 (en) 2001-12-03 2004-07-13 Novo Nordisk A/S Glucagon antagonists
WO2003053938A1 (en) 2001-12-20 2003-07-03 Novo Nordisk A/S Benzimidazols and indols as glucagon receptor antagonists/inverse agonisten
US20030212119A1 (en) 2001-12-20 2003-11-13 Jesper Lau Novel glucagon receptor antagonists/inverse agonists
US20060116366A1 (en) 2002-12-04 2006-06-01 Parmee Emma R Spirocyclic ureas, compositions containing such compounds and methods of use
MY141521A (en) 2002-12-12 2010-05-14 Hoffmann La Roche 5-substituted-six-membered heteroaromatic glucokinase activators
US20040152750A1 (en) 2002-12-20 2004-08-05 Kodra Janos Tibor Novel glucagon antagonists
US7572922B2 (en) 2003-01-27 2009-08-11 Merck & Co., Inc. Substituted pyrazoles, compositions containing such compounds and methods of use
US7138529B2 (en) * 2003-04-16 2006-11-21 Hoffmann-La Roche Inc. Substituted 3-cyanothiophene acetamides as glucagon receptor antagonists
CN1774435A (en) 2003-04-21 2006-05-17 第一制药株式会社 Five-membered heterocyclic derivative
AU2004238240A1 (en) 2003-05-09 2004-11-25 Merck & Co., Inc. Benzimidazoles, compositions containing such compounds and methods of use
CA2546601A1 (en) 2003-11-19 2005-06-09 Metabasis Therapeutics, Inc. Novel phosphorus-containing thyromimetics
US20070054902A1 (en) 2003-12-02 2007-03-08 Shionogi & Co., Ltd. Isoxazole derivatives as peroxisome proliferator-activated receptors agonists
AU2004312001B2 (en) 2003-12-19 2009-08-27 Merck & Co., Inc. Cyclic guanidines, compositions containing such compounds and methods of use
US20070015757A1 (en) 2003-12-19 2007-01-18 Novo Nordisk A/S Novel Glucagon Antagonists/Inverse Agonists
EP1758859B1 (en) 2004-05-28 2013-07-17 Eli Lilly And Company Glucagon receptor antagonists, preparation and therapeutic uses
PL1756064T3 (en) 2004-06-04 2008-11-28 Merck Sharp & Dohme Pyrazole derivatives, compositions containing such compounds and methods of use
DK1758853T3 (en) 2004-06-14 2010-04-06 Lilly Co Eli Glucagon Receptor Antagonists, Preparation and Therapeutic Uses
EP1768954A4 (en) * 2004-06-24 2008-05-28 Incyte Corp 2-methylpropanamides and their use as pharmaceuticals
WO2006017055A2 (en) 2004-07-07 2006-02-16 Merck & Co., Inc. Pyrazole amide derivatives, compositions containing such compounds and methods of use
CA2574147A1 (en) 2004-07-22 2006-02-09 Linda Brockunier Substituted pyrazoles, compositions containing such compounds and methods of use
PL1856090T3 (en) 2005-02-11 2010-02-26 Lilly Co Eli Substituted thiophene derivatives as glucagon receptor antagonists, preparation and therapeutic uses
US8318760B2 (en) 2005-03-21 2012-11-27 Merck Sharp & Dohme Corp. Substituted aryl and heteroaryl derivatives, compositions containing such compounds and methods of use
US7803951B2 (en) 2005-03-30 2010-09-28 Merck Sharp & Dohme Corp. Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
KR100738004B1 (en) 2005-05-23 2007-07-13 (주)주빅스테크놀러지 Hybrid Peer To Peer Network Intelligent Distributed Compiler System and Method thereof, and Computer Readable Recording Medium on which a Program therefor is recorded
EP1910303A2 (en) 2005-07-26 2008-04-16 Merck & Co., Inc. Process for synthesizing a substituted pyrazole
TW200745031A (en) 2005-10-13 2007-12-16 Merck & Co Inc Acyl indoles, compositions containing such compounds and methods of use
JP5198280B2 (en) 2005-11-17 2013-05-15 イーライ リリー アンド カンパニー Glucagon receptor antagonists and their preparation and therapeutic use
EP1951661B1 (en) 2005-11-17 2012-08-08 Eli Lilly And Company Glucagon receptor antagonists, preparation and therapeutic uses
BRPI0618484A2 (en) 2005-11-18 2011-08-30 Lilly Co Eli compound or a pharmaceutically acceptable salt thereof, pharmaceutical composition, methods to inhibit the glucagon receptor in a mammal, to selectively reduce the glycemic level in a mammal and to treat type 2 diabetes, and, use of a compound or a salt thereof
BRPI0618140A2 (en) 2005-11-22 2011-08-16 Lilly Co Eli pharmaceutically acceptable compound or salt thereof, pharmaceutical composition, and use of a compound or salt thereof
DK1957484T3 (en) 2005-11-23 2010-05-10 Lilly Co Eli Glucagon Receptor Antagonists, Preparation and Therapeutic Uses
AU2007229850A1 (en) 2006-03-23 2007-10-04 Merck & Co., Inc. Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
JP2009537525A (en) 2006-05-16 2009-10-29 メルク エンド カムパニー インコーポレーテッド Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
US7512570B2 (en) 2006-05-30 2009-03-31 Zaracom Technologies Inc. Artificial intelligence analyzer and generator
JP5258563B2 (en) 2006-06-29 2013-08-07 日産化学工業株式会社 Alpha amino acid derivatives and pharmaceuticals containing them as active ingredients
TW200821284A (en) 2006-10-03 2008-05-16 Merck & Co Inc Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
JP5455636B2 (en) * 2006-12-02 2014-03-26 ソウル ナショナル ユニバーシティー インダストリー ファンデーション Aryl compounds, hydrates thereof, solvates thereof, stereoisomers thereof, or pharmaceutically acceptable salts thereof, methods for producing aryl compounds, and uses of aryl compounds, etc.
JP5322951B2 (en) 2007-02-09 2013-10-23 リガンド・ファーマシューティカルズ・インコーポレイテッド Novel antagonist of glucagon receptor
KR101599089B1 (en) 2008-08-13 2016-03-02 메타베이시스 테라퓨틱스, 인크. Glucagon antagonists
WO2013012959A1 (en) 2011-07-18 2013-01-24 Tokai Pharmaceuticals, Inc. Novel compositions and methods for treating prostate cancer

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003048109A1 (en) * 2001-12-03 2003-06-12 Novo Nordisk A/S Novel glucagon antagonists
WO2004002480A1 (en) * 2002-06-27 2004-01-08 Novo Nordisk A/S Novel glucagon antagonists/inverse agonists

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KURUKULASURIYA, R. ET AL.: "Biaryl amide glucagon receptor antagonists", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 14, no. 9, 2004, pages 2047 - 2050, XP002339903, ISSN: 0960-894X, DOI: 10.1016/J.BMCL.2004.02.056 *
ROSOWSKY, A. ET AL.: "METHOTREXATE ANALOGUES 32. CHAIN EXTENSION ALPHA CARBOXYL DELETION AND GAMMA CARBOXYL REPLACEMENT BY SULFONATE AND PHOSPHONATE EFFECT ON ENZYME BINDING AND CELL-GROWTH INHIBITION", JOURNAL OF MEDICINAL CHEMISTRY, vol. 31, no. 7, 1988, pages 1326 - 1331, XP002301095, ISSN: 0022-2623, DOI: 10.1021/JM00402A012 *

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